Ginsenoside CK regulates non-alcoholic fatty liver disease by regulating liver fat metabolism and gut microbiota.

Abstract

The global incidence of non-alcoholic fatty liver disease (NAFLD) is on a continuous rise, characterized by hepatic lipid metabolism disorder and gut microbiota dysbiosis. Although ginsenoside compound K (CK) exhibits hepatoprotective and anti-inflammatory activities, its specific role in the pathogenesis of NAFLD remains to be fully elucidated. In this study, a high-fat-high-cholesterol (HFHC) diet-induced NAFLD mouse model was used to investigate the protective effects of CK against the disease. The results demonstrated that CK intervention significantly attenuated HFHC diet-induced body weight gain in mice: the body weight of mice in the CK-L group (60 mg/kg) decreased by approximately 11.7%, hepatic inflammation was reduced by about 35%-45%, and lipid deposition was improved by roughly 50%-60%. Mechanistically, CK activates the peroxisome proliferator-activated receptor (PPAR) signaling pathway, regulates the expression of lipid metabolism-related genes and proteins, thereby ameliorating lipid metabolism disorder. Meanwhile, CK reverses HFHC diet-induced gut microbiota dysbiosis, upregulates the abundance of the beneficial bacterium Akkermansia, and modulates the intestinal phylum composition in NAFLD mice by increasing the proportion of Bacteroidetes and decreasing that of Firmicutes. CK regulates the occurrence and development of NAFLD via the gut-liver axis, providing experimental evidence for subsequent mechanistic research on NAFLD prevention and treatment as well as the exploration of candidate drugs.